Anti-CTLA-4 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-10844137-B2
Application number	US-201816046551-A
Country	US
Kind code	B2
Filing date	Jul 26, 2018
Priority date	Jul 27, 2017
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

The present invention provides antibodies that bind to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to CTLA-4. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing CTLA-4 activity, thus providing a means of activating T-cells and/or for treating a disease or disorder such as cancer or viral infection.

First claim

What is claimed is:

1. An antibody or antigen-binding fragment thereof that binds specifically to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 194; and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 202.

2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains comprising, respectively, the amino acid sequences of SEQ ID NOs: 196-198-200-204-206-208.

3. The antibody or antigen-binding fragment of claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR/LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 194/202.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody.

5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a fully human antibody.

6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a human IgG1 heavy chain constant region.

7. The antibody or antigen-binding fragment of claim 1 that is an antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 509.

8. The antibody or antigen-binding fragment of claim 1 that is an antibody comprising a heavy chain and a light chain, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 510.

9. The antibody or antigen-binding fragment of claim 1 that is an antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 509 and the light chain comprises the amino acid sequence of SEQ ID NO: 510.

10. A fully human monoclonal antibody that binds specifically to CTLA-4 comprising a heavy chain comprising the amino acid sequence of residues 1-445 of SEQ ID NO: 509 and a light chain comprising the amino acid sequence of SEQ ID NO: 510.

11. The fully human monoclonal antibody of claim 10 comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 509 and a light chain comprising the amino acid sequence of SEQ ID NO: 510.

12. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable carrier or diluent.

13. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 2 , and a pharmaceutically acceptable carrier or diluent.

14. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 3 , and a pharmaceutically acceptable carrier or diluent.

15. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 4 , and a pharmaceutically acceptable carrier or diluent.

16. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 5 , and a pharmaceutically acceptable carrier or diluent.

17. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 6 , and a pharmaceutically acceptable carrier or diluent.

18. A pharmaceutical composition comprising an antibody of claim 7 , and a pharmaceutically acceptable carrier or diluent.

19. A pharmaceutical composition comprising an antibody of claim 8 , and a pharmaceutically acceptable carrier or diluent.

20. A pharmaceutical composition comprising an antibody of claim 10 , and a pharmaceutically acceptable carrier or diluent.

Assignees

• Regeneron Pharma

Inventors

• Hermann Aynur
• Ioffe Ella
• Burova Elena
• Thurston Gavin
• Olson William

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/2887

  against CD20 · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title